Can nerve damage in multiple sclerosis (MS) be reversed? Within what time frame would a therapy be effective? How long do patients have before their disease is too advanced to treat?
New research by Manzoor Bhat, M.S., Ph.D., of UT Health San Antonio, has yielded interesting clues. The findings, reported in the July 11 issue of the Journal of Neuroscience, suggest therapy is feasible but there might be a limited time window to treat nerve damage in MS.
What is multiple sclerosis?
Multiple sclerosis, a disease of the central nervous system, affects more than 2 million people worldwide. Neurons, the core component of the nervous system, fire electrical impulses that are carried to other neurons and distant muscles. It is this impulse propagation that underlies our cognition, sensory functions and ability to move. Neurons conduct information through axons, which are long, trunk-like structures insulated by a protective sheath, called myelin. As the neuronal signal reaches the end of the axonal terminal, it continues its path by being further relayed to other neurons or muscles.
In MS, a person’s own immune system damages the axons’ myelin sheath. Healthy myelin enables the signals to travel faster along the axons. When the sheath is injured, the signal conductance slows down dramatically, leading to debilitating health conditions and even full disability.
Mice with missing gene become immobile
The San Antonio researchers study mice that have a deficiency in structures called the nodes of Ranvier. These nodes are gaps in the myelin sheath that function like gatekeepers and amplifiers, allowing the electrical impulses to proceed in a fast and efficient manner through the network to their respective targets.
A gene named beta IV-Spectrin, which makes the beta IV-Spectrin protein, helps in the formation and maintenance of the nodes of Ranvier. Mutant mice lacking beta IV-Spectrin form immature nodes that fall apart over time. These mice develop deficiency in mobility, and by 6 months of age become essentially paralyzed.
Strategy restored gene and prevented full paralysis
Julia Saifetiarova, Ph.D., a postdoctoral fellow in Dr. Bhat’s laboratory, used a genetic strategy to restore the beta IV-Spectrin gene in beta IV-Spectrin mutants. This genetic approach prevented full paralysis in rescued animals. Gene restoration at earlier stages, before severe disability, resulted in greater improvement, compared to restoration at later stages, when the symptoms have progressed.
“We found out that if you reverse the node disintegration early on, you get a better outcome, and if you reverse it later, there is mild recovery,” Dr. Bhat said. “This is because the myelinated axons themselves become damaged and unhealthy if they don’t have functional nodes, and thus are not able to conduct or propagate nerve impulses.”
It is known that nerve damage leads to muscle atrophy in MS patients. Dr. Bhat’s team is also interested in learning whether muscles’ recovery is attainable if the nerve functions are restored.
Additional work needed
The sooner scientists like Dr. Bhat and Dr. Saifetiarova can understand what impact MS has on myelinated axons and how to reverse the damage—such as repairing the myelin sheath and rebuilding the nodes of Ranvier—the sooner a therapy could be developed and tested to provide better functional outcomes to patients.
“Our mouse model allows us a unique opportunity to determine the changes that take place over time in myelinated nerve fibers after injury, and to perform studies after nerve functions have been restored,” Dr. Bhat said.
Zachry Foundation support
Dr. Bhat is the Zachry Foundation Distinguished Chair in Neurosciences at UT Health San Antonio. He is professor and chairman of the Department of Cellular and Integrative Physiology in the university’s Joe R. and Teresa Lozano Long School of Medicine.
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